Immunohistochemical Analysis Reveals Increased Active Gsk3 and Inactive Pp2a Levels in Anaplastic Thyroid Cancer Publisher



Bahari F ; Mossahebimohammadi M ; Samimi H ; Sharifi F ; Rakhshkhorshid H ; Naderi M ; Tavangar SM ; Mahmoodzadeh H ; Nili F ; Haghpanah V
Source: Journal of Diabetes and Metabolic Disorders Published:2025

Abstract

Objectives: Anaplastic thyroid carcinoma (ATC) is a lethal subtype of thyroid cancer with a poor prognosis. Due to the lack of promising treatment opportunities for ATC, gaining a better understanding of the molecular mechanisms underlying tumorigenesis seems crucial. Here, we focused on two major players in the Wnt signaling pathway. Methods: The expression of PP2A and GSK3α/β proteins was studied in 12 ATC and 15 goiter formalin-fixed paraffin-embedded tissue samples using immunohistochemistry. The intensity of nuclear staining in tumor cells, as well as the total scores of protein expression, were calculated. Results: The expression of inactive PP2A and active GSK3α/β proteins was negative in all control (goiter) samples. Both proteins were expressed in all ATC samples at different levels. Notably, eight samples represented strong expression (percentage = 100; total score = 300) of both proteins. The average total score staining was 210.3 for the phosphorylated and active form of GSK3α/β (Y279/216) and 274.5 for phosphorylated PP2A at Y307 and its inactive form. For features such as age, gender, greatest diameter of tumors, as well as PP2A and GSK3α/β total staining scores, no significant differences were observed between metastatic and nonmetastatic cases. Similarly, no association was demonstrated between metastasis with demographic and tumor characteristics. Conclusions: The current study investigated the expression of PP2A and GSK3α/β, two key proteins in the Wnt signaling pathway, in ATC tissue samples. Although this study highlights the importance of PP2A and GSK3α/β in ATC, a clear understanding of PP2A and GSK3α/β dysregulation and function in ATC remains to be elucidated. © 2025 Elsevier B.V., All rights reserved.